A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1513-1522 ◽  
Author(s):  
T. Akasaka ◽  
M. Kanno ◽  
R. Balling ◽  
M.A. Mieza ◽  
M. Taniguchi ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Transcriptional Repression ◽  
Ectopic Expression ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Paraxial Mesoderm ◽  
Gene Products ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Polycomb Group Gene

Segment identity in both invertebrates and vertebrates is conferred by spatially restricted distribution of homeotic gene products. In Drosophila, the expression of Homeobox genes during embryogenesis is initially induced by segmentation gene products and then maintained by Polycomb group and Trithorax group gene products. Polycomb group gene homologs are conserved in vertebrates. Murine mel-18 and closely related bmi-1 are homologous to posterior sex combs and suppressor two of zeste. Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences. To gain further insight into the function of Mel-18, we have inactivated the mel-18 locus by homologous recombination. Mice lacking mel-18 survive to birth and die around 4 weeks after birth after exhibiting strong growth retardation. Similar to the Drosophila posterior sex combs mutant, posterior transformations of the axial skeleton were reproducibly observed in mel-18 mutants. The homeotic transformations were correlated with ectopic expression of Homeobox cluster genes along the anteroposterior axis in the developing paraxial mesoderm. Surprisingly, mel-18-deficient phenotypes are reminiscent of bmi-1 mutants. These results indicate that the vertebrate Polycomb group genes mel-18 and bmi-1, like Drosophila Polycomb group gene products, might play a crucial role in maintaining the silent state of Homeobox gene expression during paraxial mesoderm development.

Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1587-1597 ◽  
Author(s):  
T. Akasaka ◽  
M. van Lohuizen ◽  
N. van der Lugt ◽  
Y. Mizutani-Koseki ◽  
M. Kanno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Subsequent Development ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Gene Products ◽  
Hox Gene ◽  
Hox Cluster ◽  
Polycomb Group Genes ◽  
Mediate Cell

Polycomb group genes were identified as a conserved group of genes whose products are required in multimeric complexes to maintain spatially restricted expression of Hox cluster genes. Unlike in Drosophila, in mammals Polycomb group (PcG) genes are represented as highly related gene pairs, indicative of duplication during metazoan evolution. Mel18 and Bmi1 are mammalian homologs of Drosophila Posterior sex combs. Mice deficient for Mel18 or Bmi1 exhibit similar posterior transformations of the axial skeleton and display severe immune deficiency, suggesting that their gene products act on overlapping pathways/target genes. However unique phenotypes upon loss of either Mel18 or Bmi1 are also observed. We show using embryos doubly deficient for Mel18 and Bmi1 that Mel18 and Bmi1 act in synergy and in a dose-dependent and cell type-specific manner to repress Hox cluster genes and mediate cell survival of embryos during development. In addition, we demonstrate that Mel18 and Bmi1, although essential for maintenance of the appropriate expression domains of Hox cluster genes, are not required for the initial establishment of Hox gene expression. Furthermore, we show an unexpected requirement for Mel18 and Bmi1 gene products to maintain stable expression of Hox cluster genes in regions caudal to the prospective anterior expression boundaries during subsequent development.

Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products

Development ◽  
1992 ◽  
Vol 114 (2) ◽  
pp. 493-505 ◽  
Author(s):  
J. Simon ◽  
A. Chiang ◽  
W. Bender
Keyword(s):  
Expression Patterns ◽  
Ectopic Expression ◽  
Specific Pattern ◽  
Polycomb Group ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Normal Expression ◽  
Sex Comb ◽  
Regulatory Dna ◽  
Pair Rule

Mutations in genes of the Polycomb (Pc) group cause abnormal segmental development due to ectopic expression of the homeotic products of the Antennapedia and bithorax complexes. Here the requirements for Pc group genes in controlling the abdA and AbdB products of the bithorax complex are described. Embryos containing mutations in the genes Polycomb (Pc), extra sex combs (esc), Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb-like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs (Psc) and pleiohomeotic (pho) were examined. In every case, both abdA and AbdB are expressed outside of their normal domains along the anterior-posterior (A-P) axis, consistent with these Pc group products acting in a single pathway or molecular complex. The earliest detectable ectopic expression is highest in the parasegments immediately adjacent to the normal expression boundary. Surprisingly, in the most severe Pc group mutants, the earliest ectopic AbdB is distributed in a pair-rule pattern. At all stages, ectopic abdA in the epidermis is highest along the anterior edges of the parasegments, in a pattern that mimics the normal abdA cell-specific pattern. These examples of highly patterned mis-expression show that Pc group mutations do not cause indiscriminate activation of homeotic products. We suggest that the ectopic expression patterns result from factors that normally activate abdA and AbdB only in certain parasegments, but that in Pc group mutants these factors gain access to regulatory DNA in all parasegments.

Involvement of the Polycomb-group geneRing1Bin the specification of the anterior-posterior axis in mice

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4171-4183 ◽  
Author(s):  
Maki Suzuki ◽  
Yoko Mizutani-Koseki ◽  
Yu-ichi Fujimura ◽  
Hiro Miyagishima ◽  
Tomomi Kaneko ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Hox Genes ◽  
Protein Complexes ◽  
Mouse Genome Informatics ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Chromosomal Dna ◽  
Polycomb Group Genes ◽  
Group Protein

The products of the Polycomb group of genes form complexes that maintain the state of transcriptional repression of several genes with relevance to development and in cell proliferation. We have identified Ring1B, the product of the Ring1B gene (Rnf2 – Mouse Genome Informatics), by means of its interaction with the Polycomb group protein Mel18. We describe biochemical and genetic studies directed to understand the biological role of Ring1B. Immunoprecipitation studies indicate that Ring1B form part of protein complexes containing the products of other Polycomb group genes, such as Rae28/Mph1 and M33, and that this complexes associate to chromosomal DNA. We have generated a mouse line bearing a hypomorphic Ring1B allele, which shows posterior homeotic transformations of the axial skeleton and a mild derepression of some Hox genes (Hoxb4, Hoxb6 and Hoxb8) in cells anterior to their normal boundaries of expression in the mesodermal compartment. By contrast, the overexpression of Ring1B in chick embryos results in the repression of Hoxb9 expression in the neural tube. These results, together with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are consistent with a role for Ring1B in the regulation of Hox gene expression by Polycomb group complexes.

Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 805-810 ◽  
Author(s):  
D. Moazed ◽  
P.H. O'Farrell
Keyword(s):  
Expression Pattern ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Polycomb Group Genes ◽  
Sex Combs ◽  
Segment Polarity ◽  
Selector Genes ◽  
Stable Maintenance

The stable maintenance of expression patterns of homeotic genes depends on the function of a number of negative trans-regulators, termed the Polycomb (Pc) group of genes. We have examined the pattern of expression of the Drosophila segment polarity gene, engrailed (en), in embryos mutant for several different members of the Pc group. Here we report that embryos mutant for two or more Pc group genes show strong ectopic en expression, while only weak derepression of en occurs in embryos mutant for a single Pc group gene. This derepression is independent of two known activators of en expression: en itself and wingless. Additionally, in contrast to the strong ectopic expression of homeotic genes observed in extra sex combs- (esc-) mutant embryos, the en expression pattern is nearly normal in esc- embryos. This suggests that the esc gene product functions in a pathway independent of the other genes in the group. The data indicate that the same group of genes is required for stable restriction of en expression to a striped pattern and for the restriction of expression of homeotic genes along the anterior-posterior axis, and support a global role for the Pc group genes in stable repression of activity of developmental selector genes.

scholarly journals Homeotic transformations of the axial skeleton of YY1 mutant mice and genetic interaction with the Polycomb group gene Ring1/Ring1A

2006 ◽  
Vol 123 (4) ◽  
pp. 312-320 ◽  
Author(s):  
Mar Lorente ◽  
Claudia Pérez ◽  
Carmen Sánchez ◽  
Mary Donohoe ◽  
Yang Shi ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Mutant Mice ◽  
Polycomb Group Gene

Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway

2004 ◽  
Vol 323 (2) ◽  
pp. 523-533 ◽  
Author(s):  
Norihisa Shindo ◽  
Atsushi Sakai ◽  
Kouji Yamada ◽  
Toru Higashinakagawa
Keyword(s):  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Polycomb Group ◽  
Hedgehog Signaling Pathway ◽  
Sex Combs ◽  
Polycomb Group Gene

Genetic interactions and dosage effects of Polycomb group genes in mice

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3543-3551 ◽  
Author(s):  
S. Bel ◽  
N. Core ◽  
M. Djabali ◽  
K. Kieboom ◽  
N. Van der Lugt ◽  
...  
Keyword(s):  
Hox Genes ◽  
Expression Patterns ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Genetic Interactions ◽  
Homeotic Gene ◽  
Polycomb Group Genes ◽  
Dosage Effects ◽  
Somitic Mesoderm ◽  
Homeotic Gene Expression

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes. These skeletal transformations are accompanied with an enhanced shift of the anterior limit of expression of several Hox genes in the somitic mesoderm. Our results demonstrate that in mice the Polycomb group genes act in synergy to control the nested expression pattern of some Hox genes in somitic mesodermal tissues during development.

scholarly journals Transcriptional repression by Drosophila and mammalian Polycomb group proteins in transfected mammalian cells.

1994 ◽  
Vol 14 (3) ◽  
pp. 1721-1732 ◽  
Author(s):  
C A Bunker ◽  
R E Kingston
Keyword(s):  
Binding Sites ◽  
Transcriptional Repression ◽  
Fusion Proteins ◽  
Mammalian Cells ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Related Gene ◽  
Activation Domains ◽  
Sex Combs ◽  
Significant Homology

The Polycomb group (Pc-G) genes are essential for maintaining the proper spatially restricted expression pattern of the homeotic loci during Drosophila development. The Pc-G proteins appear to function at target loci to maintain a state of transcriptional repression. The murine oncogene bmi-1 has significant homology to the Pc-G gene Posterior sex combs (Psc) and a highly related gene, Suppressor two of zeste [Su(z)2]. We show here that the proteins encoded by bmi-1 and the Pc-G genes Polycomb (Pc) and Psc as well as Su(z)2 mediate repression in mammalian cells when targeted to a promoter by LexA in a cotransfection system. These fusion proteins repress activator function by as much as 30-fold, and the effect on different activation domains is distinct for each Pc-G protein. Repression is observed when the LexA fusion proteins are bound directly adjacent to activator binding sites and also when bound 1,700 bases from the promoter. These data demonstrate that the products of the Pc-G genes can significantly repress activator function on transiently introduced DNA. We suggest that this function contributes to the stable repression of targeted loci during development.

scholarly journals Needs and Targets for the multi sex combs Gene Product in Drosophila melanogaster

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1823-1838 ◽  
Author(s):  
Olivier Saget ◽  
Françoise Forquignon ◽  
Pedro Santamaria ◽  
Neel B Randsholt
Keyword(s):  
Drosophila Melanogaster ◽  
Ectopic Expression ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Maternal Control ◽  
Gap Gene ◽  
Sex Combs ◽  
Normal Expression ◽  
Selector Genes ◽  
Mutant Phenotypes

Abstract We have analyzed the requirements for the multi sex combs (mxc) gene during development to gain further insight into the mechanisms and developmental processes that depend on the important trans-regulators forming the Polycomb group (PcG) in Drosophila melanogaster. mxc is allelic with the tumor suppressor locus lethal (1) malignant blood neoplasm (l(1)mbn). We show that the mxc product is dramatically needed in most tissues because its loss leads to cell death after a few divisions. mxc has also a strong maternal effect. We find that hypomorphic mxc mutations enhance other PcG gene mutant phenotypes and cause ectopic expression of homeotic genes, confirming that PcG products are cooperatively involved in repression of selector genes outside their normal expression domains. We also demonstrate that the mxc product is needed for imaginal head specification, through regulation of the ANT-C gene Deformed. Our analysis reveals that mxc is involved in the maternal control of early zygotic gap gene expression previously reported for some PcG genes and suggests that the mechanism of this early PcG function could be different from the PcG-mediated regulation of homeotic selector genes later in development. We discuss these data in view of the numerous functions of PcG genes during development.

E(z): a polycomb group gene or a trithorax group gene?

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2189-2197 ◽  
Author(s):  
D. LaJeunesse ◽  
A. Shearn
Keyword(s):  
Polycomb Group ◽  
Bithorax Complex ◽  
Trithorax Group ◽  
Polycomb Group Genes ◽  
Enhancer Of Zeste ◽  
Selector Genes ◽  
Homeotic Selector Genes ◽  
Polycomb Group Gene ◽  
Anterior Posterior ◽  
Homeotic Selector

The products of the Polycomb group of genes are cooperatively involved in repressing expression of homeotic selector genes outside of their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of Polycomb group genes results in the ectopic expression of both Antennapedia Complex and Bithorax Complex genes. The products of the trithorax group of genes are cooperatively involved in maintaining active expression of homeotic selector genes within their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of trithorax group genes results in reduced expression of both Antennapedia Complex and Bithorax Complex genes. Although Enhancer of zeste has been classified as a member of the Polycomb group, in this paper we show that Enhancer of zeste can also be classified as a member of the trithorax group. The requirement for Enhancer of zeste activity as either a trithorax group or Polycomb group gene depends on the homeotic selector gene locus as well as on spatial and temporal cues.

Sign in / Sign up

Export Citation Format

Share Document